Melanocytes are cells located in the basal layer of the epidermis that produce the pigment melanin. The melanocyte-specific enzyme, tyrosinase (TYR), is required for the rate-limiting step of melanin synthesis while two other members of the tyrosinase family, tyrosinase related protein 1 (TRP1) and dopachrome tautomerase (DCT), regulate the type of melanin synthesized. Once melanin is produced, it is stored in melanosomes, which are transferred from melanocytes to keratinacytes, thus giving skin its characteristic color. Disruption of normal melanocyte function can lead to skin cancer and other skin diseases that affect the level of pigmentation.
Hyperpigmentation is a common condition in which patches of skin become darker in color than the surrounding skin. Hyperpigmentation can affect the skin color of people of any skin tone. Possible causes of hyperpigmentation include pregnancy, Addison's disease, sun exposure, age, and certain drugs. Abnormal production of melanin can result in a number of hyperpigmentation disorders. As one example, melasma is a dysfunction of melanin production that results in irregular brown hyperpigmentation. Although the cause of melasma is not completely understood, common contributing factors include a genetic predisposition, dark complexion, pregnancy, use of oral contraceptives, endocrine disorders, hormone treatments, and exposure to ultraviolet light. In addition, some cosmetics and medications have also been linked to the development of melasma. As another example, solar lentigo is characterized by hyperpigmented lesions (sun spots) that range in size from a few millimeters to more than a centimeter in diameter and are associated with sun exposure. As another example, lentigo senilis (LS) is the skin condition of age spots characterized by enhanced epidermal pigmentation with an increase in the number of tyrosinase-positive melanocytes.
Because of their tendency to recur, hyperpigmentary conditions are often difficult to treat. Current treatment options for hyperpigmentation include chemical peels, laser resurfacing, intense pulse light therapy, and bleaching creams such as hydroquinone or arbutin. The use of topical hydroquinone is the most common treatment for many of these conditions. A predominant mechanism for the skin lightening effects of hydroquinone is through inhibition of tyrosinase activity. Chemical peels, laser treatments, and intense pulsed light therapy are additional therapeutic options. However, these options have adverse side effects such as skin irritation and hypopigmentation of surrounding skin. There is also concern about the safety of long term use of hydroquinone, which is a potential carcinogen. Thus, there is a need in the art for the development of additional and improved therapeutic options for hyperpigmentary conditions.